Alkylene oxide polymer compositions

ABSTRACT

Alkylene oxide polymer compositions having particular molecular weight distributions are disclosed. As a result of the molecular weight distributions, the disclosed alkylene oxide polymer compositions are suitable, among other things, for the manufacture of films, e.g., for use in manufacturing soft gel capsules. Capsules made from the disclosed alkylene oxide polymer compositions can provide enhanced resistance to crosslinking often caused by liquid filling materials, e.g., polyethylene glycol, used in gelatin capsule manufacture.

This appln is a 371 of PCT/US99/02526 filed Feb. 5, 1999 which claimbenefit of provisional No. 60/073,872 filed Feb. 6, 1998.

FIELD OF THE INVENTION

The present invention relates to alkylene oxide polymer compositions.More specifically, the present invention relates to alkylene oxidepolymer compositions having molecular weight distributions suitable forthe manufacture of films, e.g., water soluble, flexible films for use assoft gel capsules.

BACKGROUND OF THE INVENTION

Gelatin is a protein material produced by hydrolysis of collagen fromanimal bones and connective tissues. Gelatin has served as anencapsulating material, a coating for pills, an emulsifying agent, acoating for photographic materials, a bacterial culture medium, acomponent of printers' rollers and hectograph plates, an ingredient ofpopular desserts, and for many other widely varied uses.

One common use for gelatin is in the manufacture of soft gel capsulesfor the delivery of active ingredients. Although gelatin is generallystrong and tough, its extensibility and flexibility are generally low.In addition, since gelatin is derived from animal sources, there areoften inconsistencies in product quality from batch to batch. Thephysical and chemical properties of gelatin are a function of the sourceof the collagen, method of manufacturing, conditions during extractionand concentration, thermal history, pH and the chemical nature ofimpurities and additives. Moreover, during storage, gelatin oftenundergoes a crosslinking reaction which in turn changes the dissolutioncharacter and the drug bio-availability characteristics. This shortensthe useful life of the gelatin. Thus, mechanical failures of gelatinsoft gel capsules are often encountered. Additionally, the use of animalderived materials, such as gelatin, has come under regulatory review dueto concerns regarding the transmission of animal based illness.

Accordingly, new materials are desired which can function asreplacements for gelatin, particularly gelatin based films useful formanufacturing soft gel capsules and the like.

SUMMARY OF THE INVENTION

By the present invention, problems commonly associated with the use ofgelatin in manufacturing films, used for example in manufacturing softgel capsules, have been solved. More specifically, films manufacturedusing the polymer compositions of the present invention can haveenhanced stability, processability and physical and chemical propertiesas compared to films made from gelatin.

In accordance with the present invention, alkylene oxide polymercompositions having certain molecular weight distributions are provided.Advantageously, the polymer compositions of the present invention arewater soluble. However, quite surprisingly, films made from thecompositions of the present invention are substantially insoluble inaqueous polyethylene glycol solutions, a liquid often used as aphysiologically acceptable carrier, when such solutions contain about 25wt. % water or less. As a result of the high water tolerance of thefilms, capsules made from these films can accommodate increased amountsof active ingredients, e.g., acetaminophen, in the capsule. Inaccordance with the present invention, enhancements in the concentrationof the active ingredients in the fill can often be up to 30 percent ormore as compared to a comparable gelatin capsule.

DETAILED DESCRIPTION OF THE INVENTION

The alkylene oxide polymers of the present invention are prepared fromalkylene oxide monomers containing from about 1 to 5 carbon atoms permolecule, e.g., ethylene oxide or propylene oxide, as well as copolymersand derivatives thereof. Alkylene oxide monomers suitable for use asstarting materials are commercially available.

Preferably, the alkylene oxide polymers of the present inventioncomprise ethylene oxide polymers. The ethylene oxide polymers include,for example, homopolymers of ethylene oxide and copolymers of ethyleneoxide with one or more polymerizable comonomers. The particularcomonomer is not critical to the present invention and may containhydrocarbon substituents, such as, for example, alkyl, cycloalkyl,aromatic, alkene (also referred to as alkylene) or branched alkyl oralkene groups; provided, however, that the water solubility orwater-dispersibility is maintained. Further details concerning thepreparation of ethylene oxide polymers is known in the art. See forexample, U.S. Pat. No. 2,969,403 issued to Helmut et al., U.S. Pat. No.3,037,943 issued to Bailey et al., U.S. Pat. No. 3,167,519 issued toBailey et al., U.S. Pat. No. 4,193,892, issued to Goeke et al. and U.S.Pat. No. 4,267,309 issued to Goeke et al.

The desired molecular weight distribution of the alkylene oxide polymersof the present invention can be obtained by polymerizing the alkyleneoxide monomers directly or by blending alkylene oxide polymers havingdifferent molecular weight ranges. For polymers having a molecularweight of less than 50,000 grams per gram mole (“g/gmol”), as usedherein, the term “molecular weight” means number average molecularweight (sometimes referred to herein as “M_(n)”). For polymers having amolecular weight of 50,000 g/gmol or higher, as used herein, the term“molecular weight” means weight average molecular weight (sometimesreferred to as “M_(w)”). Techniques for determining the averagemolecular weight are known to those skilled in the art. A suitabletechnique to determine number average molecular weight is by end grouptitration and a suitable technique to determine the weight averagemolecular weight is by light scattering.

Often in the art, alkylene oxide polymers having molecular weights ofabout 50,000 and higher are referred to as polyalkylene oxides, e.g.,polyethylene oxide, and alkylene oxide polymers having molecular weightsof less than about 50,000 are referred to as polyalkylene glycols, e.g.,polyethylene glycol. Polyalkylene oxides and polyalkylene glycols arecommercially available, for example, from Union Carbide Corporation,Danbury, Conn., under the tradenames POLYOX® Water Soluble Resins andCARBOWAX® polyethylene glycols (PEG), respectively. Preferably, variouspolyalkylene glycols and polyalkylene oxides are blended in appropriateproportions to achieve the desired molecular weight distribution of thealkylene oxide polymer compositions of the present invention.

In accordance with the present invention, the alkylene oxide polymercompositions typically comprise from 1 to about 25 wt. %, more typicallyfrom 1 to about 19 wt. %, preferably from about 2 to 19 wt. %, and morepreferably from about 3 to 18 wt. % of alkylene oxide polymer having amolecular weight of about 100 to 2,000 g/gmol, typically 100 to 1,000g/gmol.

The alkylene oxide polymer compositions further typically comprise fromabout 10 to 60 wt. %, more typically from about 10 to 50 wt. %,preferably from about 20 to 45 wt. % and more preferably from about 25to 35 wt. % of alkylene oxide polymer having a molecular weight of fromabout 1,000 to 50,000 g/gmol, typically about 2000 to 50,000 g/gmol andpreferably from about 1,000 to 25,000 g/gmol.

Additionally, the alkylene oxide polymer compositions of the presentinvention typically comprise from about 25 to 89 wt. %, preferably fromabout 30 to 75 wt. %, more preferably from about 35 to 70 wt. % and mostpreferably from about 45 to 65 wt. % of alkylene oxide polymer having amolecular weight of from about 50,000 to 10,000,000 g/gmol, preferablyfrom about 100,000 to 4,000,000 g/gmol.

Unless otherwise indicated, the weight percentages of the variousmolecular weight fractions are based on the total weight of the alkyleneoxide polymer composition, e.g., including water, other polymers andadditives as hereinafter described. The alkylene oxide polymercompositions of the present invention may comprise one or more alkyleneoxide polymers within each molecular weight range. For instance, in oneaspect of the invention, the alkylene oxide polymer compositioncomprises an alkylene oxide polymer having a molecular weight of 1,450g/gmol and an alkylene oxide polymer having a molecular weight of about8,000 g/gmol, both of which are within the more broadly stated range ofabout 1,000 to 50,000 g/gmol.

The alkylene oxide polymer compositions of the present invention maycomprise additional polymers in order to achieve desired properties.Such other polymers include, for example, naturally occurring andsynthetic neutral, cationic, anionic and amphoteric polymers, e.g.,polysaccharides and derivatives thereof, hyaluronic acid, otherpolyalkylene oxides, linked or cross linked polyalkylene oxides withlinkers like epoxides, polyvinyl pyrrolidones, polycaprolactones,polyvinyl acetates and polycarboxylic acids, copolymers of alkyleneoxide, acrylic acid and vinyl acetate. The polysaccharides includenaturally occurring, biosynthesized and derivatized carbohydratepolymers and mixtures thereof. Such materials encompass high molecularweight polymers composed of monosaccharide units joined by glycosidicbonds. These materials may include, for example, the entire starch andcellulose families; pectin, chitosan; chitin; the seaweed products suchas agar and carrageenan; alginate; the natural gums such as guar, arabicand tragacanth; bio-derived gums such as xanthan; and the like. Commonpolysaccharides include cellulosics conventionally employed for thepreparation of cellulose ethers, such as, for example, chemical cotton,cotton linters, wood pulp, alkali cellulose and the like. Such materialsare commercially available. The molecular weight of the polysaccharidestypically ranges from about 10,000 to 2,000,000 grams per gram mole.Preferably, the polysaccharides are etherified by reacting thepolysaccharide with an alkylene oxide, e.g., ethylene oxide, propyleneoxide or butylene oxide or otherwise derivatized by techniques known tothose skilled in the art.

When such other polymers are used in the compositions of the presentinvention, they are typically present in amounts of from 1 to about 20wt. %, and more typically from about 2 to 15 wt. % based on the totalweight of the alkylene oxide polymer composition.

Preferably, the alkylene oxide polymer compositions of the presentinvention comprise water in an amount of from 1 to about 20 wt. %, morepreferably from 1 to about 10 wt. % and most preferably from about 3 to8 wt. % based on the total weight of the alkylene oxide polymercomposition. Preferably, water is present in an amount effective toequilibrate with the amount of moisture in the air or other environmentin which the compositions are stored, particularly when the compositionsare used to manufacture films, e.g., gel capsules, as hereinafterdescribed.

Other additives may be present in the alkylene oxide polymercompositions of the present invention in amounts from about 5 parts permillion by weight (“ppmw”) to about 15 wt. % often about 10 wt. % orless, based on the total weight of the composition. Typically, otheradditives comprise for example, preservatives, antioxidants, colorants,opaquing agents and the like.

In one aspect of the invention, the alkylene oxide compositions of thepresent invention contain minor amounts, e.g., less than about 20 wt. %based on the total weight of the composition, of gelatin. Morepreferably, there is a substantial absence, e.g., less than about 5 wt.%, preferably less than about 1 wt. % based on the total weight of thecomposition, of gelatin.

The alkylene oxide compositions of the present invention may be providedin any desired form. Typical forms include, for example, liquids, smallparticles, e.g., 0.001 to about 100 microns, large particles orgranules, e.g., about 1 to 10 millimeters (“mm”), extrudates, tablets,films and capsules.

The alkylene oxide polymer compositions of the present invention areparticularly suitable for manufacturing films. Typically, prior tomaking the films, polymers having the desired molecular weights arefirst uniformly blended along with water in a conventional mixer such asa V blender, Hobart mixer, or ball mill, e.g., for about 60 minutes. Apreferred composition is comprised of 5.4 wt. % of CARBOWAX® PEG 300(M_(w)=300 g/gmol), 8.1 wt. % of CARBOWAX® PEG 1450 (M_(w)=1450), 27 wt.% of CARBOWAX® PEG 8000 (M_(w)=8000), 54 wt. % of POLYOX® WSR N-750(M_(w)=300,000) and 5.5 wt. % water. Details concerning the manufactureof films comprising the alkylene oxide polymers of the present inventionare known to those skilled in the art.

Preferably, films made from the alkylene oxide polymer compositions ofthe present invention have thicknesses of from about 0.05 to 1.0 mm andpreferably from about 0.1 to 0.5 mm. Typically, the films are flexible,i.e., not rigid, and are water soluble, disperse or disintegrate rapidlyin water. As used herein, the term “water soluble” means that at leastone gram and preferably two grams of the alkylene oxide polymercomposition are soluble in 100 grams of distilled water at 25° C. andone atmosphere.

Preferably, the films made from the alkylene oxide polymer compositionsof the present invention have desirable properties in terms offlexibility, toughness, uniformity and clarity. Typically, themechanical properties of the films prepared by the alkylene oxidepolymer compositions of the present invention have the followingmechanical properties. The tensile strength of extruded and thermalpressed films, as measured in accordance with ASTM Method 412-68, is atleast about 200 psi or more with an elongation of at least about 50%.Normally, the air blown films have about 20% lower tensile strength.Furthermore, the films are preferably sealable. That is, the filmsshould be able to seal onto themselves with the help of elevatedtemperature, pressure, or both, with or without the help of a diluteaqueous solution of one of the ingredients of the film. Further detailsconcerning the sealing of ethylene oxide polymer films are known in theart. See for example, U.S. Pat. No. 3,999,358 issued to Lewis, et al.

Quite surprisingly, the alkylene oxide polymer compositions of thepresent invention are substantially insoluble in polyalkylene glycolsand aqueous polyethylene glycol solutions (molecular weight equal to 400g/gmol) containing up to about 25 wt. % water. As used herein, the term“substantially insoluble” means that less than about 5 wt. %, preferablyless than about 3 wt. % and more preferably less than about 1 wt. % ofthe polymer dissolves in the solution at 25° C. and one atmosphere overa time period of 10 minutes. This unexpected property provides asolution to the problem of mechanical failures associated with gelatinsoft gel capsules where the liquids used inside the capsules oftenadversely affect the integrity of the capsule walls. More specifically,polyalkylene glycols, e.g., polyethylene glycol, are often used as theliquid filling material in soft gel capsules because they arephysiologically acceptable carriers. Polyethylene glycol has a highinfinity for the gelatin capsules and softeners often used in preparingsoft shell gelatin capsules. As a result, the gelatin capsules canundergo a crosslinking reaction which changes the dissolution characterand drug bio-availability characteristics.

Thus, a preferred use for the alkylene oxide polymer compositions of thepresent invention is in the manufacture of soft gel capsules. Quiteadvantageously, the alkylene oxide compositions of the present inventioncan replace gelatin in the manufacture of soft shell capsules. Ingeneral, the soft shell capsules can be prepared by a rotary die processin which they are formed, filled, and sealed in a single operation. Theyare filled with a solution or suspension of drug or die in liquids thatwill not solubilize the shell.

The compositions of the present invention can also be used tomanufacture hard shell capsules which are generally rigid. The hardshell capsules comprise two, fitted cap and body pieces. The rigidity ofthe capsule can be increased by increasing the amount of the highmolecular weight polymer fractions and/or decreasing the low molecularweight polymer fractions. They can be made by a punch and die operationthat is carried out at above the softening temperature of the polymer,e.g., 50 to 80° C.

In general, the capsules of the present invention, both hard shell andsoft gel, comprise a continuous, flexible wall having an outer surfaceand an inner surface. The wall is comprised of a film made from thealkylene oxide polymer compositions of the present invention. The innersurface of the capsule at least partially surrounds the inner space ofthe capsule.

Further details concerning the manufacture of gel capsules andappropriate apparatus useful in manufacturing such capsules are known inthe art, such as described in U.S. Pat. No. 4,028,024 issued toMoreland.

The size of the capsules can be determined by those skilled in the artdepending upon the intended use. For example, capsules for oral drugdelivery for humans will typically have a size ranging from about 1 mmto 10 mm. In contrast, capsules for oral drug delivery for animals maybe significantly larger, e.g., about 10 mm to 30 mm. Capsules used forother purposes, such as, for example, in the manufacture of paint ballsmay be relatively large, whereas capsules used to contain ink or otherfluids may be extremely small. Thus, typically the size of the capsuleswill range from about 1 mm to 50 mm. In the case of non-sphericalcapsules, e.g., elliptically shaped capsules, the above mentioneddiameter is made with reference to the largest dimension perpendicularto the longitudinal axis.

The capsules of the present invention may or may not contain a fillingor material within the inner space of the capsule. When the capsulescontain a filling, such filling can be a liquid, gas, semi-solid, solidor gel. The particular form of the filling is not critical to thepresent invention.

Often, liquid fillings are employed in the capsules of the presentinvention. Preferably, the liquid used as the filling material does notadversely affect the integrity of the capsule wall. More specifically,it is preferred that the liquid does not promote the dissolution of thecapsule wall or cause the capsule wall to crosslink over time.Typically, the interior space of the capsule will be at least 10 percentby volume filled with liquid, preferably at least 25 percent, morepreferably at least 50 percent and most preferably at least 75 volumepercent filled.

Those skilled in the art will recognize that the capsules of the presentinvention will have a variety of industrial and personal care uses. Forinstance, the capsules can be used for the oral delivery ofpharmaceutically active agents to humans and animals. In addition, thecapsules can be used in personal care applications, e.g., hair care andskin care formulations, to deliver oils, vitamins, proteins, polymersand other personal care ingredients. The capsules can also be used, forexample, to provide bath oil beads, fragrances and time releasedingredients. Further, the capsules can be used in the manufacture ofpaint balls and other recreational products. Moreover, the capsules canbe employed in a variety of industrial uses, such as, for example, inthe delivery of inks, catalysts, initiators, enzymes, and the like. Theamount of the particular active ingredient utilized depends on theparticular end use. Typically, the amount of active ingredient willrange from about 0.01 to 99 wt. % based on the total weight of thefilling material, e.g., liquid and active. As used herein, the term“active ingredient” means the ingredient or ingredients introduced intothe capsule to achieve the desired effect upon delivery. Whether sucheffect is pharmacological, chemical, cosmetic, physical or otherwise isnot critical to the present invention. Further details concerning theselection and amounts of the appropriate filling materials and activeingredients can be determined by those skilled in the art.

One preferred end use for the capsules of the present invention is forthe delivery of active ingredients in pharmaceutical and personal careapplications. For such applications, the liquid material comprises aphysiologically acceptable carrier, preferably a polyalkylene glycol,more preferably polyethylene glycol having a weight average molecularweight of about 100 to 500, preferably about 400 g/gmol. Morepreferably, the filling material comprises an aqueous, polyalkyleneglycol solution comprising from about 1 to 30 wt. %, typically fromabout 5 to 25 wt. %, preferably from about 10 to 25 wt. % and morepreferably from about 15 to 25 wt. % water, based on the total weight ofthe liquid, e.g., polyalkylene glycol plus water.

Typical actives for personal care applications, i.e., bothpharmaceutical and cosmetic, include but are not limited to spermicides,virucides, analgesics, anesthetics, antibiotic agents, antibacterialagents, antiseptic agents, vitamins, corticosteriods, antifungal agents,vasodilators, hormones, antihistamines, autacoids, decongestants,bronchodilators and other antiasthmatic agents, beta-blockers,anti-nauseants, antiemetics, anticonvulsants, kerolytic agents,anti-diarrhea agents, anti-alopecia agents, anti-inflammatory agents,exfoliating agents, sunscreens, anti-oxidants, enzymes, anti-infectionagents. Typical pharmaceutically active ingredients suitable for use inthe invention include acetaminophen, famotidine, chlorpheniramine,pseudoephedrine, dectromethorphan, diphenhydramine, brompheniramine,phenylpropanolamine, clemastine, terfenadine, astemizole,pharmaceutically acceptable salts thereof and mixtures thereof.

Other components of the liquid filling material can be determined bythose skilled in the art and include materials, such as for example,solvents, diluents and adjuvants such as, for example, ethyl alcohol,isopropyl alcohol, higher alcohols, glycerine, propylene glycol,sorbitol, preservatives, surfactants, menthol, eucalyptus oil, otheressential oils, fragrances, viscosity adjusters, and the like.

The concentration of the active ingredient in the capsule is, of course,dependent on the particular end use and the active agent, which can bedetermined by those skilled in the art. For example, thepharmaceutically active ingredients are usually present in the capsulein a therapeutically effective amount which produces the desiredtherapeutic response upon administration. In determining such amounts,the particular compound being administered, the bio-availabilitycharacteristics of the compound, the dose regiment, the age and weightof the patient, and other factors must be considered.

The following Examples are provided for illustrative purposes and arenot intended to limit the scope of the claims which follow. Theconcentrations of ingredients are provided in weight percent unlessotherwise indicated.

The designations and abbreviations used in the Examples are defined asfollows:

POLYOX ® WSR N 750 An ethylene oxide polymer having a molecular weightof about 300,000 g/gmol, available from Union Carbide Corporation,Danbury, CT. POLYOX ® WSR N 10 An ethylene oxide polymer having amolecular weight of about 100,000 g/gmol, available from Union CarbideCorporation, Danbury, CT. CARBOWAX ® PEG An epoxide linked polyethyleneglycol Compound 20M having a molecular weight of about 18,000 g/gmol,available from Union Carbide Corporation, Danbury, CT. CARBOWAX ® PEG8000 A polyethylene glycol having a molecular weight of about 8,000g/gmol, available from Union Carbide Corporation, Danbury, CT.CARBOWAX ® MPEG 5000 A methoxy polyethylene glycol having a molecularweight of about 5,000 g/gmol, available from Union Carbide Corporation,Danbury, CT. CARBOWAX ® PEG 1450 A polyethylene glycol having amolecular weight of about 1450 g/gmol, available from Union CarbideCorporation, Danbury, CT. CARBOWAX ® PEG 400 A polyethylene glycolhaving a molecular weight of about 400 g/gmol, available from UnionCarbide Corporation, Danbury, CT. CARBOWAX ® PEG 300 A polyethyleneglycol having a molecular weight of about 300 g/gmol, available fromUnion Carbide Corporation, Danbury, CT. CELLOSIZE ® HEC QP-40Hydroxyethyl cellulose having a molecular weight of about 120,000g/gmol, available from Union Carbide Corporation, Danbury, CT. TONE ®Polymer P-767 A polycaprolactone resin having a molecular weight ofabout 35,000 to 55,000 g/gmol, available from Union Carbide Corporation,Danbury, CT. PVAc GB 101 A vinyl acetate polymer having a molecularweight of about 40,000 g/gmol, available from Union Carbide Corporation,Danbury, CT. PVP (Polyvinylpyrrolidone) A 1-ethynyl-2-pyrrolidinonepolymer

The following test procedures define the performance tests used in theevaluation.

The tensile strength measurements were conducted on an InstronExtensometer employing ASTM Method D 412-68. Film dissolution studieswere conducted by a visual and a gel permeation chromatographic (GPC)method. A piece of the film with known weight (0.05 to 0.5 gram) wasadded to 10 grams of water or an aqueous PEG solution. The time it tookto dissolve the film was recorded. If the film did not dissolve in over42 hours, the observation was stopped. The liquid phase was sampledperiodically and analyzed by GPC to detect the presence of components ofthe film in the solution.

Films were viewed under Scanning Electron Microscope (SEM) for theiruniformity and microstructure.

EXAMPLE 1 Preparation of Composite

The composites were prepared in batches of 300 grams of total material.The blending was carried out in two steps. First, solid polymer powderssuch as POLYOX®, PEG 8000 and other polymers (as set forth in Examples 4and 5) for desired properties were milled in a one quart ball mill for30 minutes. To this blend, a water solution of PEG 300 and PEG 1450 wasadded with additional mixing. KITCHENAID and HOBART mixers were used forblending the composites of larger size (500 to 5000 grams). Theresulting wet granular blend was then extruded as described in Examples2 and 3.

EXAMPLE 2 Air Blown Extrusion Process

A composite sample, as prepared in Example 1, was fed to a heatedcircular die using a single screw Brabender extruder (Model #11505). Theextruder chamber was furnished with a three zone electric heating andcontrol system. The blend was heated to about 125° C. prior to enteringthe circular die. With the help of air that was blowing from the centerof the die, the hot extruded film was blown into a cylindrical shape.After it had cooled, the film was rolled on a take-up roller that waslocated about three feet from the die. The film thickness was about 0.2mm.

EXAMPLE 3 Slot Cast Die Extrusion and Pressing Process

A wet granular mass, as prepared in Example 1, was fed to a 2″ wide slotcast die using a single screw Brabender extruder (Model #11505). Theextruder chamber was furnished with a three zone electric heating andcontrol system. In the extruder chamber, the composite was heated to125° C. before it was extruded from the die. The die body was heated toabout 125° C. The thickness of the tape from the slot cast die was inthe range of 1 to 2.5 mm. The tape was cooled on a moving belt and takenup on a roller. Using a CARVER® press, pieces from the extruded tapewere pressed to about 0.2 mm thick films between two electrically heatedplates,. This operation was carried out at about 2000 pound and 100° C.The film pieces, thus produced, were subjected to physical propertiesevaluation such as strength, dissolution, permeability, sealing, etc.

EXAMPLE 4 Flexible Lip Ribbon Die Extrusion

A wet granular mass, as prepared in Example 1, was fed to a electricallyheated 3″ flexible lip ribbon die using a single stage mixing screwBrabender Extruder (Model # PL2000-6 with Plati-Corder data processingsystem). The extruder chamber was furnished with a four zone electricheating and control system. The composite was fed to the extruder withthe help of a single screw volumetric feeder. In the extruder chamber,the composite was heated to 120° C. before it was fed to the die. Thedie was heated to about 120° C. The semi-solid film from the die waspicked up by a film take-off system which had three adjustable gap drumsequipped with temperature monitoring and control capabilities.. Afterpassing between the drums, the film was air cooled and rolled on a 2.5″diameter roller. The film thickness was controlled by a combination ofadjustments between the die-lip gap, the drum gap, and the speed of thetake-off system. The film thickness was maintained between 0.2 to 0.4mm. Thermo-mechanical properties consisting of melt behavior and creepbehavior were measured for these films using DSC (differential scanningcalorimeters) TA 2920 and TMA 2940 respectively. The DSC melt curveindicated that the softening starts at about 50° C., and the meltingoccurs at about 62° C.

EXAMPLE 5 Alkylene Oxide Polymer Compositions

a) The following films were made according to procedures described inExamples 1 and 2.

TABLE 1 Composition and Properties of Air Blown Films Quantity TensileNo. Component (wt. %) Strength (psi) 1. POLYOX ® WSR N-750 54 885 PEGCompound 20M 27 PEG 1450 8.0 PEG 300 5.5 Water 5.5 2. POLYOX ® WSR N-75051.2 877 PEG Compound 20M 25.7 PVAc (GB 101) 5.2 PEG 1450 7.5 PEG 3005.3 Water 5.1 3. POLYOX ® WSR N-750 48.4 825 PEG Compound 20M 24.2 PVAc(GB 101) 9.6 PEG 1450 7.5 PEG 300 5.3 Water 5.1

b) The following films were made according to procedures described inExamples 1 and 3.

TABLE 2 Composition and Properties of Extruded and Pressed FilmsQuantity Tensile No. Component (wt. %) Strength (psi) 1. POLYOX ®WSRN-750 54 1205 PEG 8000 27 PEG 1450 8.0 PEG 300 5.5 Water 5.5 2.POLYOX ® WSR N-750 54 1120 MPEG 5000 27 PEG 1450 8.0 PEG 300 5.5 Water5.5 3. POLYOX ® WSR N-750 51.4  796 PEG 8000 25.7 PEG 1450 7.6 PEG 3005.3 PVAc (GB 101) 4.76 Water 5.24 4. POLYOX ® WSR N-750 51.4 1073 PEG8000 25.7 PEG 1450 7.6 PEG 300 5.3 PVP 4.76 Water 5.24 5. POLYOX ® WSRN-750 51.4 1237 PEG 8000 25.7 PEG 1450 7.6 PEG 300 5.3 WSR N-10 4.76Water 5.24 6. POLYOX ® WSR N-750 51.4 1235 PEG 8000 25.7 PEG 1450 7.6PEG 300 5.3 PCL 161 4.76 Water 5.24 7. POLYOX ® WSR N-750 51.4 1139 PEG8000 25.7 PEG 1450 7.6 PEG 300 5.3 HEC QP-40 4.76 Water 5.24

A 0.2 mm thick film of all polymer blends in Tables 1 and 2 abovedissolved in 100% water within 2 to 10 minutes, however, they wereinsoluble in PEG 400 containing 0 to 25 wt.% water. They dissolved inaqueous PEG 400 solution containing 50% or more water, but, thedissolution rate was significantly slower than in 100% water anddepended on water concentration in the solution.

Comparative Examples

The following compositions were prepared according to Example 1 but werenot readily extrudable or incapable of being extruded or otherwiseprovided undesirable properties.

TABLE 3 Quantity No. Component (wt. %) Observations 1. POLYOX ® WSRN-750 6.3 Paste like PEG Compound 20M 33.1 PEG 400 55.0 Water 5.0 2.POLYOX ® WSR N-3000 92 tough will not mold PEG Compound 20M 3 or pressPEG 1450 1.8 PEG 300 1.2 Water 2 3. POLYOX ® WSR N-750 5.2 brittle, lowstrength PEG 8000 75.8 PEG 1450 6.2 PEG 300 4.3 Water 8.5 4. POLYOX ®WSR N-750 31.8 extremely tacky PEG Compound 20M 31.8 PEG 400 31.8 Water4.6 5. POLYOX ® WSR N-3000 90 difficult to mold or PEG Compound 20M 5press PEG 1450 1.8 PEG 300 1.2 Water 2 6. POLYOX ® WSR N-750 25 brittle,low strength PEG 8000 60 PEG 1450 7.6 PEG 300 5.3 Water 2.1

FLEXIBLE LIP RIBBON DIE EXTRUDED FILMS

The following films were made according to Examples 1 and 4.

TABLE 4 Composition Properties of Flexible Lip Die Extruded FilmsTensile Quantity Elongation Strength No. Component (wt. %) (% at 25° C.)(psi) 1. POLYOX ® WSR N-750 54 200 994 PEG 8000 27 PEG 1450 8.0 PEG 3005.6 Water 5.4 2. POLYOX ® WSR N-750 54 650 935 MPEG 5000 27 PEG 1450 8.0PEG 300 5.6 Water 5.4 3. POLYOX ® WSR N-750 49 700 993 MPEG 5000 32 PEG1450 8.0 PEG 300 5.6 Water 5.4 4. POLYOX ® WSR N-750 44 350 1498  MPEG5000 37 PEG 1450 8.0 PEG 300 5.6 Water 5.4 5. POLYOX ® WSR N-750 49.0250 972 MPEG 5000 27.0 MPEG 2000 5.0 PEG 1450 8.0 PEG 300 5.6 Water 5.46. POLYOX ® WSR N-750 51.3 400 1127  MPEG 5000 26.5 PVAc (GB 101) 5.0PEG 1450 7.6 PEG 300 5.3 Water 5.2 7. POLYOX ® WSR N-750 54.0 300 953PEG 8000 17.0 PEG 3350 10.0 PEG 1450 8.0 PEG 300 5.6 Water 5.4 8.POLYOX ® WSR N-750 38.0 100 830 PEG 8000 38.0 POLYOX ® WSR N-1105 5.0PEG 1450 8.0 PEG 300 5.6 Water 5.4

In addition to the specific aspects of the invention described above,those skilled in the art will recognize that other aspects of theinvention are intended to be included within the scope of the claimswhich follow. For example, the alkylene oxide polymer compositions ofthe present invention may comprise other ingredients, monomers andpolymers in addition to those specifically described herein. Also, thecompositions of the present invention may have utility for other usesthan those specifically described herein.

We claim:
 1. An alkylene oxide polymer composition characterized in thatsaid polymer composition has a molecular weight distribution as follows:(a) from about 1 to 19 weight percent based on the total composition ofa polymer fraction having a number average molecular weight of fromabout 100 to 2000 g/gmol; (b) from about 10 to 60 weight percent basedon the total composition of a polymer fraction having a number averagemolecular weight of from about 1000 to 50,000 g/gmol; (c) from about 25to 89 weight percent based on the total composition of a polymerfraction having a weight average molecular weight of from about 50,000to 10,000 g/gmol; with the proviso that polymer fraction (a) and polymerfraction (b) do not have the same molecular weight.
 2. The compositionof claim 1 wherein from about 2 to 18 weight percent based on the totalcomposition has a number average molecular weight of from about 100 to1000 g/gmol.
 3. The composition of claim 1 wherein from about 20 to 55weight percent based on the total composition has a number averagemolecular weight of from about 1000 to 30,000 g/gmol.
 4. The compositionof claim 1 wherein from about 35 to 70 weight percent based on the totalcomposition has a weight average molecular weight of from about 100,000to 4,000,000 g/gmol.
 5. The composition of claim 1 wherein furthercomprising from about 1 to 10 weight percent water.
 6. The compositionof claim 1 further comprising at least one other synthetic or naturallyoccurring polymer.
 7. The composition of claim 6 wherein the otherpolymer is selected from the group consisting of polysaccharides andderivatives thereof, polyvinyl pyrrolidones, polycaprolactones,polyvinylacetates polycarboxylic acids and mixtures thereof.
 8. The compositionof claim 1 in the form of particles, granules, extrudates, tablets orcapsules.
 9. The composition of claim 1 in form of a film.
 10. Thecomposition of claim 1 which is substantially insoluble in aqueoussolution of polyethylene glycol having a number average molecular weightof about 400 g/gmol comprising about 25 weight percent water or less.11. A capsule comprising: (i) a continuous wall having an outer surfaceand an inner surface, said wall comprised of an alkylene oxide polymercomposition having a molecular weight distribution as follows; (a) fromabout 1 to 19 weight percent based on the total composition of a polymerfraction having a number average molecular weight of from about 100 to2000 g/gmol; (b) from about 10 to 60 weight percent based on the totalcomposition of a polymer fraction having a number average molecularweight of from about 1000 to 50,000 g/gmol; (c) from about 25 to 89weight percent based on the total composition of a polymer fractionhaving a weight average molecular weight of from about 50,000 to 10,000g/gmol; with the proviso that polymer fraction (a) and polymer fraction(b) do not have the same molecular weight; and (ii) an inner space atleast partially surrounded by said inner surface.
 12. The capsule ofclaim 11 wherein said polymer composition further comprises from about 1to 10 weight percent water based on the total composition.
 13. Thecapsule of claim 11 wherein said inner space comprises a liquid.
 14. Thecapsule of claim 13 wherein said liquid comprises a physiologicallyacceptable carrier.
 15. The capsule of claim 14 wherein said liquidcomprises an aqueous solution of a polyalkylene glycol.
 16. The capsuleof claim 15 wherein the aqueous solution comprises about 25 weightpercent water or less.